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Showing papers on "Lanosterol synthase published in 1994"


Journal ArticleDOI
TL;DR: Two overlapping clones were assembled to make a functional reconstruction of the ERG7 gene, which contains a 2196-bp open reading frame capable of encoding an 83-kDa protein, and the reconstruction complemented the erg7 mutation when driven from either its native promoter or the strong ADH1 promoter.
Abstract: We report the cloning, characterization, and overexpression of Saccharomyces cerevisiae ERG7, which encodes lanosterol synthase [(S)-2,3-epoxysqualene mutase (cyclizing, lanosterol forming), EC 5.4.99.7], the enzyme responsible for the complex cyclization/rearrangement step in sterol biosynthesis. Oligonucleotide primers were designed corresponding to protein sequences conserved between Candida albicans ERG7 and the related Arabidopsis thaliana cycloartenol synthase [(S)-2,3-epoxysqualene mutase (cyclizing, cycloartenol forming), EC 5.4.99.8]. A PCR product was amplified from yeast genomic DNA using these primers and was used to probe yeast libraries by hybridization. Partial-length clones homologous to the two known epoxysqualene mutases were isolated, but a full-length sequence was found neither in cDNA nor genomic libraries, whether in phage or plasmids. Two overlapping clones were assembled to make a functional reconstruction of the gene, which contains a 2196-bp open reading frame capable of encoding an 83-kDa protein. The reconstruction complemented the erg7 mutation when driven from either its native promoter or the strong ADH1 promoter.

104 citations


Journal ArticleDOI
TL;DR: Treatment of HepG2 cells with a cyclase inhibitor such as 8-azadecalin does not lead to an intracellular accumulation of repressor molecules high enough to fully trigger a regulatory pathway resulting in a complete down-regulation of HMG-CoA reductase, and a synergistic mode of action of these inhibitors seems plausible.

35 citations


Journal ArticleDOI
TL;DR: In this paper, the authors reported the synthesis of (6E)-8-thia-2,3-oxidosqualene (22) and (14E)-13-thia -2, 3-oxidsqualene-lanosterol cyclase inhibitors.
Abstract: Synthesis of (6E)-8-thia-2,3-oxidosqualene (22) and (14E)-13-thia-2,3-oxidosqualene (34) as inhibitors of 2,3-oxidosqualene-lanosterol cyclase are reported. Synthesis of 22 required the stereospecific generation of a vinyl sulfide. This was achieved by a new coupling of a benzenethiosulfonate (15) and a lithiated vinyl iodide (18). Synthesis of 34 involved similar coupling of benzenethiosulfonate 29 with lithium reagent obtained from vinyl iodide 33. The required (E)-vinyl iodides 18 and 33 were prepared by zirconium-catalyzed carboalumination of 4-pentyn-1-ol, (16) and 2,6-dimethyl-2(E),6(E)-dien-10-yne (32) respectively. Both 22 and 34 inhibited 2,3-oxidosqualene-lanosterol cyclase from Candida albicans with IC 50 values of 0.68 and 45 μM, respectively

30 citations